PubMed Health⌕ Search

Biomedical subjects

B A Navia

Publications and source records attributed to B A Navia.

At least 19 recordsLinked to original sources
PubMed1998

Increased cerebral blood volume in HIV-positive patients detected by functional MRI.

OBJECTIVE: To study changes in cerebral hemodynamics related to HIV infection. BACKGROUND: Cerebral injury is a well-known manifestation of HIV infection. Physiologic changes in the HIV brain may precede structural changes and may be detected by functional MRI (fMRI). METHODS: Dynamic contrast fMRI was used to measure the cerebral blood volume (CBV) in 13 patients infected with HIV and in 7 healthy control subjects. RESULTS: Significant increases in dynamic CBV were found in the deep (p < 0.001) and cortical gray matter (p < 0.05) of HIV-positive (HIV+) patients. Patients with definite cognitive impairment showed significantly greater increases in CBV in the deep gray matter (DGM) compared with those without impairment. In one patient with rapidly progressive cognitive impairment, these abnormalities reversed and paralleled clinical improvement after initiation of zidovudine monotherapy. CONCLUSIONS: This study supports the hypothesis that HIV infection is associated with significant cerebral hemodynamic changes, particularly in the DGM, that may contribute to cognitive dysfunction in AIDS. Functional MRI may be useful for early detection of cerebral injury and for the assessment of novel therapies.

Adult↗
PubMed1998

A phase I/II trial of nimodipine for HIV-related neurologic complications.

BACKGROUND: Few effective treatments are available for AIDS dementia complex (ADC) and HIV-associated neuropathy. However, recent in vitro studies indicate that nimodipine, a voltage-dependent calcium channel antagonist, can prevent HIV-related neuronal injury and may provide a novel form of treatment for these disorders. METHODS: To determine the safety and possible efficacy of this agent, 41 patients with mild to severe ADC, including 19 patients with neuropathy, were entered into the AIDS Clinical Trial Group multicenter, phase-I and phase-II study. Nimodipine at 60 mg p.o., five times daily; 30 mg p.o., three times daily; or placebo was administered for 16 weeks as adjuvant treatment to antiretroviral therapy. RESULTS: Neuropsychological performance at baseline, measured by the composite neuropsychological Z score (NPZ-8), correlated significantly with the ADC stage and with CSF levels of neopterin, a marker of immune activation. No significant differences in toxicity were observed among the three arms. Intent-to-treat analysis showed no significant change in the NPZ-8, although improvement was suggested in the high-dose arm. In addition, a trend toward stabilization in peripheral neuropathy was observed in both nimodipine arms compared with placebo. CONCLUSIONS: Nimodipine and other similar nonantiretroviral agents may provide a safe and promising avenue of treatment for neurologic disorders associated with HIV infection. The results of this study indicate that further clinical trials are warranted.

AIDS Dementia Complex↗
PubMed1997

Functional imaging of the AIDS dementia complex and the metabolic pathology of the HIV-1-infected brain.

The AIDS-dementia complex remains one of the more common neurologic disorders associated with human immunodeficiency virus (HIV) infection. Despite several advances that have been made in elucidating some of its clinical and biological features, pathogenesis is not well understood, and effective treatments are scarce. This article reveals the results of these studies and discusses how these different approaches have already enabled clinicians to study further the effects of HIV infection on brain function and to explore the functional anatomy of this important clinical syndrome.

AIDS Dementia Complex↗
PubMed1997

Clinical and biologic features of the AIDS dementia complex.

Human immunodeficiency virus type 1 infection is frequently associated with complications of the nervous system, involving all levels of the neuraxis. Many of these represent focal disorders, such as toxoplasmosis, lymphoma, and progressive multifocal leukoencephalopathy. This article reviews the salient clinical and biological features of these disorders.

AIDS Dementia Complex↗
PubMed1996

High levels of anti-HIV-1 envelope antibodies in cerebrospinal fluid as compared to serum from patients with AIDS dementia complex.

The antibody response to the HIV-1 envelope protein has not been well characterized in patients with AIDS dementia complex (ADC). We evaluated the frequency of antibodies against the HIV-1 envelope in cerebrospinal fluid (CSF) and serum from 21 persons with ADC and 10 symptom-free HIV-1-positive subjects using Western immunoblot with reducing and nonreducing buffer and radioimmunoprecipitation (RIP) analysis. RIP analysis revealed anti-envelope antibodies in all sera tested. Higher anti-envelope levels were observed in CSF than in serum of 12 of 21 ADC patients and only 1 of 10 symptom-free subjects (two-sided Fisher exact test, p < 0.05). All persons with moderate to severe ADC had higher anti-envelope levels in CSF than in sera (p < 0.005). CSF anti-gp120 antibodies were not as readily detected by Western blot analysis even under nonreduced conditions, suggesting that they are directed to conformational epitopes. Higher CSF anti-envelope antibodies appear to be more common in patients with ADC than in symptom-free HIV-1-positive subjects. This antibody pattern may serve as a marker for ADC and its progression.

AIDS Dementia Complex↗
PubMed1996

Brain choline-containing compounds are elevated in HIV-positive patients before the onset of AIDS dementia complex: A proton magnetic resonance spectroscopic study.

The CNS is frequently involved in human immunodeficiency virus (HIV) infection. In recent studies using proton magnetic resonance spectroscopy, investigators found a significant reduction in N-acetyl aspartate, a metabolic marker of neurons, in late stages of dementia. To further understand the relationship between proton magnetic resonance spectroscopy changes and clinical disease and dementia, we compared 20 HIV-infected patients presenting at varying stages of acquired immunodeficiency syndrome (AIDS) dementia complex and infection to 10 age-matched controls. We found a significant reduction in N-acetyl aspartate/creatine only in patients who had advanced dementia and CD4 counts less that 200/microliter. By contrast, a significant elevation in compounds containing choline was present in patients in the early stages of HIV infection of who had CD4 counts greater than 200/microliter, in patients with normal MRI scans, and in all AIDS dementia complex groups, including subjects with no or minimal cognitive impairment. An elevated choline level also occurred in later stages of HIV infection (CD4 < 200/microliter). Our results suggest that an increase in choline occurs before N-acetyl aspartate decrements, MRI abnormalities, and the onset of dementia, and may therefore provide a useful marker for early detection of brain injury associated with HIV infection.

AIDS Dementia Complex↗
PubMed1996

A recombination outside the BB deletion refines the location of the X linked retinitis pigmentosa locus RP3.

Genetic loci for X-linked retinitis pigmentosa (XLRP) have been mapped between Xp11.22 and Xp22.13 (RP2, RP3, RP6, and RP15). The RP3 gene, which is responsible for the predominant form of XLRP in most Caucasian populations, has been localized to Xp21.1 by linkage analysis and the map positions of chromosomal deletions associated with the disease. Previous linkage studies have suggested that RP3 is flanked by the markers DXS1110 (distal) and OTC (proximal). Patient BB was thought to have RP because of a lesion at the RP3 locus, in addition to chronic granulomatous disease, Duchenne muscular dystrophy (DMD), mild mental retardation, and the McLeod phenotype. This patient carried a deletion extending approximately 3 Mb from DMD in Xp21.3 to Xp21.1, with the proximal breakpoint located approximately 40 kb centromeric to DXS1110. The RP3 gene, therefore, is believed to reside between DXS1110 and the proximal breakpoint of the BB deletion. In order to refine the location of RP3 and to ascertain patients with RP3, we have been analyzing several XLRP families for linkage to Xp markers. Linkage analysis in an American family of 27 individuals demonstrates segregation of XLRP with markers in Xp21.1, consistent with the RP3 subtype. One affected mate shows a recombination event proximal to DXS1110. Additional markers within the DXS1110-OTC interval show that the crossover is between two novel polymorphic markers, DXS8349 and M6, both of which are present in BB DNA and lie centromeric to the proximal breakpoint. This recombination places the XLRP mutation in this family outside the BB deletion and redefines the location of RP3.

Adult↗
PubMed1993

Computer-based neuropsychological screening for AIDS dementia complex.

OBJECTIVE: To test the efficacy of reaction time (RT) measures as a screening test for AIDS dementia complex (ADC). DESIGN AND METHODS: Forty-two patients with mild-to-moderate ADC and 33 healthy HIV-1-seronegative control subjects took a computer-administered battery of four RT measures: simple RT, choice RT, and two types of sequential RT (1 and 2). RESULTS: The performance of the ADC group was significantly worse than that of the control group on all four RT measures, but not all tasks were equally sensitive. The two tests of sequential RT were found to be the best discriminators, and receiver operating characteristic curves analyses indicated that the optimal cut-off z score was 1.0 for both tests. CONCLUSIONS: These preliminary results suggest that computer-based RT, using these two measures of sequential RT, may provide a sensitive method of detecting HIV-1-associated cognitive deficits.

AIDS Dementia Complex↗
PubMed1993

Human immunodeficiency virus type 1-specific cytotoxic T lymphocytes release gamma interferon, tumor necrosis factor alpha (TNF-alpha), and TNF-beta when they encounter their target antigens.

Human immunodeficiency virus type 1 (HIV-1) infection is associated with elevated levels of inflammatory cytokines in the serum and cerebrospinal fluid of infected persons, but the sources of these proteins as well as the specific stimuli which trigger their production and release have not been fully defined. In this study, we evaluated the ability of HIV-1-specific cytotoxic T-lymphocyte (CTL) clones derived from seropositive persons to release gamma interferon (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), and TNF-beta upon contact with target cells presenting viral antigen. Peripheral blood- and cerebrospinal fluid-derived HIV-1-specific CD3+ CD4- CD8+ CTL clones as well as freshly isolated peripheral blood mononuclear cells from infected persons were tested in parallel for HIV-1-specific cytotoxicity and cytokine release. Target cells consisted of autologous and allogeneic B-lymphoblastoid cell lines sensitized with synthetic HIV-1 peptides containing the epitopes recognized by these CTL. Cytokine production was measured by specific enzyme-linked immunosorbent assay of culture supernatant fluid. HIV-1-specific CTL clones directed at envelope, Gag, reverse transcriptase, and Nef epitopes specifically released IFN-gamma, TNF-alpha, and TNF-beta upon contact with their relevant target epitopes but not following contact with irrelevant epitopes. These cytokines were released in an HLA class I-restricted fashion, and release was detectable as early as 4 to 6 h of incubation and remained elevated at 48 h. Fresh peripheral blood mononuclear cells from a seropositive person likewise released IFN-gamma in an antigen-specific and HLA class I-restricted manner when incubated with target cells presenting a peptide containing a CTL epitope, paralleling the HIV-specific cytolytic activity of these cells. These studies indicate that in addition to mediating direct cytotoxicity, HIV-1-specific CTL may affect other immune responses by releasing IFN-gamma, TNF-alpha, and TNF-beta. Elevated levels of these cytokines which have been detected in serum and cerebrospinal fluid of infected persons may be due at least in part to the persistent HIV-1-specific CTL response.

Amino Acid Sequence↗
PubMed1992

Detection of a vigorous HIV-1-specific cytotoxic T lymphocyte response in cerebrospinal fluid from infected persons with AIDS dementia complex.

AIDS dementia complex is a common neurologic disorder in later stages of HIV-1 infection. Because virus-specific CTL have been shown to contribute to neurologic disease in certain viral illnesses, we examined the cerebrospinal fluid of HIV-1-infected persons with various stages of AIDS dementia complex for the presence of HIV-1-specific CTL. In five of six subjects studied, HIV-1-specific CTL were identified in the cerebrospinal fluid. These CTL were directed at epitopes within the gag, reverse transcriptase, envelope, and nef proteins and restricted by HLA class I Ag. In four of these subjects, virus-specific CTL were detected in higher numbers in the cerebrospinal fluid compared to the peripheral blood, suggesting a specific recruitment to or local induction within the nervous system. These studies demonstrate the presence of a vigorous and broadly directed CTL response to HIV-1 in the central nervous system of infected persons with AIDS dementia complex, and provide immunologic evidence of localized intrathecal infection. Although HIV-1-specific CTL may serve to inhibit viral replication in the central nervous system, the presence of a persistent CTL response in the central nervous system may also contribute to the neurologic disorders characteristic of HIV-1 infection.

AIDS Dementia Complex↗
PubMed1987

The acquired immunodeficiency syndrome dementia complex as the presenting or sole manifestation of human immunodeficiency virus infection.

Twenty-nine patients at risk of developing acquired immunodeficiency syndrome (AIDS) presented with cognitive, motor, and behavioral dysfunctions characteristic of the AIDS dementia complex, either preceding or in the absence of major systemic opportunistic infections or neoplasms. Six of these patients were medically well, while the remainder suffered only milder manifestations of the AIDS-related complex at the time of their neurologic presentation. Over half of these patients either survived for five to 16 months or died without exhibiting systemic manifestations of AIDS. This experience indicates that the AIDS dementia complex may be the earliest, and, at times, the only evidence of human immunodeficiency infection, and that its development in this context may present a diagnostic challenge, particularly in individuals in whom risk for infection by the AIDS virus is cryptic.

Acquired Immunodeficiency Syndrome↗
PubMed1987

HIV antigen in the brains of patients with the AIDS dementia complex.

Human immunodeficiency virus infection was identified immunohistochemically in the brains of 8 patients with acquired immune deficiency syndrome dementia complex. Using a monoclonal antibody against a structural viral protein (p25), infection was detected in white matter and basal ganglia in a distribution paralleling that of the major neuropathological abnormalities. Viral antigen was identified principally in perivascular and parenchymal macrophages and in multinucleated cells of macrophage origin that were identified morphologically and by immunocytochemical staining for acid phosphatase isozyme. In 4 of the 8 patients, viral antigen was also detected in acid-phosphatase-negative, process-bearing neuroglial cells; in 2 patients, antigen was detected in basal ganglion cells that were morphologically consistent with neurons and in alkaline-phosphatase-positive cells with elongated nuclei that were most likely of endothelial origin.

Acquired Immunodeficiency Syndrome↗
PubMed1987

The metabolic pathology of the AIDS dementia complex.

A progressive dementing illness, the AIDS dementia complex (ADC) is the most frequent neurological complication of the acquired immunodeficiency syndrome. Characteristic alterations in regional cerebral metabolic rate for glucose (rCMRGlc), associated with the presence or progression of ADC, were demonstrated by [18F]fluorodeoxyglucose/positron emission tomography in 9 of 12 patients with ADC compared with 18 normal volunteer subjects. In these 9 patients, two distinct patterns of regional metabolic activity were highly correlated with intersubject gray matter rCMRGlc variation and with disease severity as assessed by neuropsychological testing. Relative subcortical (thalamus and basal ganglia) hypermetabolism was characteristic of early ADC, and disease progression was accompanied by cortical and subcortical gray matter hypometabolism.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Cerebral toxoplasmosis complicating the acquired immune deficiency syndrome: clinical and neuropathological findings in 27 patients.

We reviewed the clinical, neuroradiological, and serological findings in 27 patients with cerebral toxoplasmosis complicating the acquired immune deficiency syndrome, 19 of whom were also analyzed neuropathologically. The clinical manifestations of this disorder varied, ranging from headache and fever to coma. However, the characteristic presentation included focal neurological symptoms and signs, usually of subacute onset. In addition, two-thirds of the patients exhibited more generalized cerebral dysfunction with confusion and lethargy. The computed tomographic (CT) scan most commonly revealed ring contrast enhancement, which appeared to correlate best with the histological presence of vascular proliferation and inflammation surrounding the abscesses. However, in 5 patients the CT scan revealed either homogeneous enhancement or no enhancement, and in 3 patients the scans were negative. In general, CT scans underrepresented the number of lesions eventually documented pathologically. Double-dose contrast administration and preliminary experience with magnetic resonance imaging suggested that these techniques were superior to standard CT scanning in detecting Toxoplasma lesions. All patients were seropositive for IgG antibody against Toxoplasma gondii in blood, both before the onset of illness and at the time of presentation, although titers in some patients were as low as 1:8 and most patients did not exhibit rising titers. Prompt therapy resulted in rapid clinical improvement, documented by CT scan, associated with the development of an organizing tissue response in the host and elimination of free organisms. Response to treatment was sufficiently rapid in most patients to allow a trial of therapy as the favored approach to diagnosis.

Acquired Immunodeficiency Syndrome↗
PubMed1986

The AIDS dementia complex: I. Clinical features.

Of 70 autopsied patients with the acquired immune deficiency syndrome (AIDS), 46 suffered progressive dementia that was frequently accompanied by motor and behavioral dysfunction. Impaired memory and concentration with psychomotor slowing represented the most common early presentation of this disorder, but in nearly one half of the patients either motor or behavioral changes predominated. Early motor deficits commonly included ataxia, leg weakness, tremor, and loss of fine-motor coordination, while behavioral disturbances were manifested most commonly as apathy or withdrawal, but occasionally as a frank organic psychosis. The course of the disease was steadily progressive in most patients, and at times was punctuated by an abrupt acceleration. However, in 20% of patients a more protracted indolent course was observed. In the most advanced stage of this disease, patients exhibited a stereotyped picture of severe dementia, mutism, incontinence, paraplegia, and in some cases, myoclonus. The high incidence and unique clinical presentation of this AIDS dementia complex is consistent with the emerging concept that this complication is due to direct brain infection by the retrovirus that causes AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1986

The AIDS dementia complex: II. Neuropathology.

In order to define the histopathological substrate of the dementia that frequently complicates the acquired immune deficiency syndrome (AIDS), we analyzed the neuropathological findings in 70 autopsied adult AIDS patients, 46 of whom had suffered clinically overt dementia. Less than 10% of the brains were histologically normal. Abnormalities were found predominantly in the white matter and in subcortical structures, with relative sparing of the cortex. Their frequency and severity generally correlated well with the degree and duration of clinical dementia. Most commonly noted was diffuse pallor in the white matter, which in the pathologically milder cases was accompanied by scanty perivascular infiltrates of lymphocytes and brown-pigmented macrophages, and in the most advanced cases by clusters of foamy macrophages and multinucleated cells associated with multifocal rarefaction of the white matter. However, in nearly one third of the demented cases the histopathological findings were remarkably bland in relation to the severity of clinical dysfunction. In addition, similar mild changes were noted in over one half of the nondemented patients, consistent with subclinical involvement. Vacuolar myelopathy was found in 23 patients and was generally more common and severe in patients with advanced brain pathology. Evidence of cytomegalovirus (CMV) infection was noted in nearly one quarter of the brains and was associated with a relative abundance of microglial nodules, but correlated neither with the major subcortical neuropathology nor with the clinical dementia, indicating that CMV infection likely represented a second, superimposed process. This study establishes the AIDS dementia complex as a distinct clinical and pathological entity and, together with accumulating virological evidence, suggests that it is caused by direct LAV/HTLV-III brain infection.

Acquired Immunodeficiency Syndrome↗